Gene Expression Analysis of Human Papillomavirus-Associated Colorectal Carcinoma

Human papillomavirus (HPV) antigens had been found in colorectal cancer (CRC) tissue, but little evidence demonstrates the association of HPV with oncogene mutations in CRC. We aim to elucidate the mutated genes that link HPV infection and CRC carcinogenesis.

Cancerous and adjacent noncancerous tissues were obtained from CRC patients. HPV antigen was measured by using the immunohistochemical (IHC) technique. The differentially expressed genes (DEGs) in HPV-positive and HPV-negative tumor tissues were measured by using TaqMan Array Plates. The target genes were validated with the qPCR method.

15 (31.9%) cases of CRC patients were observed to be HPV positive, in which HPV antigen was expressed in most tumor tissues rather than in adjacent noncancerous tissues. With TaqMan Array Plates analyses, we found that 39 differentially expressed genes (DEGs) were upregulated, while 17 DEGs were downregulated in HPV-positive CRC tissues compared with HPV-negative tissues. Four DEGs (MMP-7, MYC, WNT-5A, and AXIN2) were upregulated in tumor vs. normal tissues, or adenoma vs. normal tissue in TCGA, which was overlapped with our data. In the confirmation test, MMP-7, MYC, WNT-5A, and AXIN2 were upregulated in cancerous tissue compared with adjacent noncancerous tissue. MYC, WNT-5A, and AXIN2 were shown to be upregulated in HPV-positive CRC tissues when compared to HPV-negative tissues.

HPV-encoding genome may integrate into the tumor genomes that involved in multiple signaling pathways. Further genomic and proteomic investigation is necessary for obtaining a more comprehensive knowledge of signaling pathways associated with the CRC carcinogenesis.